Anti-calmodulin autoantibody in the sera of patients with malignancies of the urogenital tract: a new antibody against a cytoskeleton-related protein.
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Biomedical subjects
Publications and source records attributed to H Oka.
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We tested the effects of calmodulin, two types of calmodulin antagonists, and various phospholipids on the phospholipase A2 activities of intact platelets, platelet membranes, and partially purified enzyme preparations. Trifluoperazine, chlorpromazine (phenothiazines) and N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7), at concentrations which antagonize the effects of calmodulin, significantly inhibited thrombin- and Ca2+ ionophore-induced production of arachidonic acid metabolites by suspensions of rabbit platelets and Ca2+-induced arachidonic acid release from phospholipids of membrane fractions, but not phospholipase A2 activity in purified enzyme preparations. The addition of acidic phospholipids, but not calmodulin, stimulated phospholipase A2 activity in purified enzyme preparations while decreasing its Km for Ca2+. The dose-response and kinetics of inhibition by calmodulin antagonists of acidic phospholipid-activated phospholipase A2 activity in purified preparations were similar to those of Ca2+-induced arachidonic acid release from membrane fractions. Calmodulin antagonists were also found to inhibit Ca2+ binding to acidic phospholipids in a similar dose-dependent manner. Our results suggest that the platelet phospholipase A2 is the key enzyme involved in arachidonic acid mobilization in platelets and is regulated by acidic phospholipids in a Ca2+-dependent manner and that calmodulin antagonists inhibit phospholipase A2 activity via an action on acidic phospholipids.
Intracellular recordings and morphological identification of neurons by means of intracellular HRP staining were performed in the midbrain-pontine tegmentum of the cat. Electrical stimulation of the substantia nigra, pars reticulata, induced short-latency inhibitory postsynaptic potentials in tegmental neurons, as previously reported. These tegmental neurons were distributed not only in the pedunculopontine tegmental nucleus (PPTN) (26 cells), but also in the cuneiform nucleus (CNF) (13 cells), the central gray substance (CG) (four cells), the parabrachial nucleus (three cells), and the tegmentum between the inferior colliculus and the CG (two cells). The morphological characteristics of the HRP-stained tegmental neurons were analyzed by camera lucida drawings of 16 well-stained cells, i.e., ten PPTN neurons, three CNF neurons, two neurons in the tegmentum between the IC/CG, and one CG neuron. All of these neurons seem to be classified as "isodendritic" neurons. Regardless of the soma size (15-120 micron in diameter), most of the tegmental neurons showed wide dendritic fields of 1-2 mm, mediolaterally, and 0.5-1 mm, dorsoventrally. These results indicate that the nigrotegmental projections exert an inhibitory influence on the neurons located in a wide variety of nuclei of the midbrain-pontine dorsal tegmentum.
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It is strongly believed that cAMP mediates histamine H2 receptor activity, but does not mediate gastrin and acetylcholine stimulation of gastric acid secretion. Therefore, cAMP production could be a marker of H2 receptor activity. Whether endogenous histamine mediates gastrin and/or acetylcholine stimulation, at least partially, remains to be elucidated. If cAMP in the gastric juice reflects H2 receptor activity, we can investigate whether endogenous histamine mediates gastrin and/or acetylcholine stimulation in vivo. In this study, we investigated whether cAMP in the gastric juice reflected histamine H2 receptor activity in the Heidenhain pouch dog in vivo using different kinds of inhibitors of gastric secretion. Our hypothesis was as follows: Upon betazole stimulation, cimetidine, an H2 receptor antagonist, should decrease cAMP output into the gastric juice, but omeprazole, an H+, K+-ATPase blocker, should not, because it blocks at a site more peripheral than the H2 receptor and the production of cAMP. Sixty minutes after betazole administration, 4.0 mumol/kg of cimetidine and 0.18 mumol/kg omeprazole were administered intravenously and they inhibited gastric juice volume to a similar degree, that is, 49.6% and 52.1%, respectively. However, omeprazole caused a greater decrease in cAMP output than cimetidine. Inhibition with 4 mumol/kg/h of cimetidine or 0.2 mumol/kg of omeprazole from the beginning of betazole stimulation also caused similar decreases in gastric juice volume, 66.6% and 60.6%, respectively. Both inhibitors decreased cAMP output into the gastric juice in a similar fashion in the first two 30 minute periods. These results do not agree with our hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Response properties of the non-pyramidal tract neurons (non-PTNs) of the kitten motor cortex were examined with intracellular horseradish peroxidase (HRP) staining under Nembutal anesthesia. Thirty-one neurons were identified as non-PTNs and their responses were analyzed with stimulation of the cerebellar nuclei (CN) and/or the medullary pyramid (Py). Excitatory postsynaptic potentials (EPSPs) were induced both by CN and Py stimulation even at birth, whereas inhibitory postsynaptic potentials (IPSPs) were first detected during the third postnatal week in layers II-III pyramidal neurons, which is much later than in PTNs. This indicates that the intracortical circuits responsible for IPSPs in the superficial cortical layers develop later than in layer V.
Based on the assumption that middle molecules that induce hepatic coma occur in the plasma of patients with fulminant hepatic failure (FHF), the authors have developed a hemodiafiltration (HDF) method using a large-pore poly(methylmethacrylate) (PMMA) membrane that allows proteins to pass through. PMMA HDF resulted in complete recovery of deep coma and long-term survival in a patient with severe FHF. Although a large-scale controlled trial is needed, PMMA HDF is believed to be promising as a future artificial liver support.
A rare case of pheochromocytoma with wide fluctuation of blood pressure at regular 7-min intervals is described. Direct blood pressure monitoring revealed periodic changes between 120/80 mmHg and 220/130 mmHg. The plasma norepinephrine concentration increased selectively in parallel with the elevation of the blood pressure. The tumor was found adjacent to the left kidney, and all abnormal data improved after its resection.
The apolipoprotein A-I (apo A-I) from the patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency has been characterized. More than 10% of total serum apo A-I was recovered in the bottom fraction (d greater than 1.21 g/ml) of the patients' sera, while in normal sera, only 4.3 +/- 2.7% (Mean +/- SD) of apo A-I was found in the bottom fraction. The lipoproteins of the sera from the patients were analysed by density gradient ultracentrifugation and by high performance liquid chromatography (HPLC). Our HPLC analysis has revealed that the association of apo A-I with a lipid-poor HDL, observed in the patients, is not due to ultracentrifugal artifacts. The serum apo A-I isoproteins and their relative concentrations in the three patients were analysed by two dimensional electrophoresis. The isoprotein distribution for each of the three patients was as follows: isoproteins 2 and 3; 12.3, 21.2 and 25.7%, suggesting that the basic isoforms (isoproteins 2 and 3) were increased compared to normal controls (3.5 + 2.3%). The profile of apo A-I isoproteins of the bottom fraction was almost the same as that of the patient's HDL, indicating the equivalent affinity of each isoprotein with lipid and/or protein of HDL. These observations are compatible with the suggestion that the reduction of HDL-cholesterol in familial LCAT deficiency may be due to rapid catabolism of HDL, resulting in the increase in the ratio of apo A-I isoprotein 2 and 3 (immature form of isoprotein A-I) to isoprotein 4 and 5 (mature form of apo A-I).
It is not clear why blood pressure rises with age in civilized countries. We examined the relationship between alcohol consumption, obesity, family history of hypertension and blood pressures at medical checkups in 534 male office workers, aged 20 to 40. The results in two age groups, 20-30 and 31-40, are as follows. Those who drank heavily (greater than 60 ml of ethanol) the previous night and/or habitual heavy drinkers (greater than 60 ml/day) had the highest blood pressure. Obese workers had higher blood pressure. Subjects with a family history of hypertension had higher blood pressure. The frequencies of heavy drinkers and obesity were higher in the group aged 31 to 40 than in the other group. These factors might contribute to the blood pressure elevation with age. 5) A histogram of the first readings of systolic blood pressure showed a bimodal distribution only in persons with a family history of hypertension.
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Using monoclonal antibodies and flow cytometry percentages and absolute number of lymphocyte populations and T cell subsets were enumerated in peripheral blood collected between 8:00 and 10:00 a.m. from 210 healthy adults. Although absolute numbers of total lymphocytes did not differ depending on age and sex, the numbers of T (Leu-4+) and natural killer (Leu-7+) cells as well as their percentages showed negative and positive correlations, respectively, with age. In Leu-7+ cells, the percentage was male-dominant irrespective of age, and the absolute number was male-dominant only in older subjects. Absolute numbers of suppressor/cytotoxic T (Leu-2a+) and helper/inducer T (Leu-3a+) cells and percentages of Leu-2a+ cells were negatively correlated with age in females. In males, only the percentage of Leu-2a+ cells was age-dependent. Leu-3a/Leu-2a was positively correlated with age in females, and was female-dominant depending on age. These results indicate that peripheral lymphocyte populations and T cell subsets vary remarkably in healthy adults even at a fixed time of day.
A 54-year-old man initially complained of frontal headache, right ear pain and tinnitus in May, 1985. This was followed by right facial palsy and hearing loss, and he was admitted to our hospital. Physical findings revealed right trigeminal nerve disturbance, left facial nerve palsy and bulbar palsy. The spinal fluid showed pleocytosis, increased protein, decreased glucose, markedly increased carcinoembryonic antigen and adenocarcinoma cells. Gastric carcinoma was revealed by an upper GI series. He was treated with chemotherapy. However, he die in August, 1985. Nodular metastases were discovered at the right internal acoustic meatus and other areas. Microscopically, signet-ring cell carcinoma had diffusely infiltrated at the subarachnoid space.
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